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[Cancer Research 61, 5366-5369, July 15, 2001]
© 2001 American Association for Cancer Research

Advances in Brief

DNA Polymerase {kappa}, Implicated in Spontaneous and DNA Damage-induced Mutagenesis, Is Overexpressed in Lung Cancer1

Jiyang O-Wang2, Kiyoko Kawamura, Yuji Tada, Haruo Ohmori, Hideki Kimura, Shigeru Sakiyama and Masatoshi Tagawa2

Divisions of Pathology [J. O-W., K. K., Y. T., S. S., M. T.] and Thoracic Diseases [H. K.], Chiba Cancer Center Research Institute, Chiba 260-8717, Japan, and Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan [H. O.]

DNA polymerase {kappa} (Pol {kappa}) is a newly identified low-fidelity polymerase implicated in spontaneous and DNA damage-induced mutagenesis. As an initial study to investigate its possible involvement in tumorigenesis, we compared the expression level of Pol {kappa} in tumors and adjacent nontumorous tissues by Northern blot, semiquantitative RT-PCR, and Western blot analyses. In this study, paired tumor and normal specimens from 29 patients with stages I to IIIb non-small cell lung cancer (NSCLC), including 13 adenocarcinomas, 15 squamous cell cancers, and 1 adenosquamous carcinoma, were analyzed, among which different levels of tumor-associated Pol {kappa} overexpression were observed in 21 of 29 matched specimens. In addition, five matched specimens exhibited elevated Pol {kappa} expression in both tumor and control tissues, whereas only one nontumorous tissue expressed a higher level of Pol {kappa} than its tumor counterpart. The preferential up-regulation of Pol {kappa} expression in tumors was highly significant (P < 0.001). There was no apparent correlation of Pol {kappa} expression levels with tumor histology, grade, and stage or with smoking history. Southern blot analysis did not show amplification of the Pol {kappa} gene, indicating that the elevated Pol {kappa} expression is likely attributable to dysregulated transcription. Our data suggest that Pol {kappa} may contribute to lung tumor development by accelerating the accumulation of mutations.




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